Cancer of the head and neck includes all cancers arising from the upper aerodigestive tract. Squamous cell carcinomas originating from mucosal surfaces represent more than 90% of cases. The incidence of head and neck squamous cell carcinoma (HNSCC) has been gradually increasing over the last three decades. It is the fifth leading cause of cancer by incidence and the sixth leading cause of cancer mortality in the world. Treatment modalities for HNSCC include surgery, radiation and chemotherapy. With advanced HNSCC, only 35% to 55% of patients survive and remain disease-free for three years, despite aggressive therapy. Locoregional recurrence develops in 30% to 40% of patients and distant metastases develop in 12% to 22%^ of patients. Palliative treatment of recurrent/metastatic HNSCC remains largely ineffective, and little progress has been made.
Although HNSCC can be considered a chemosensitive disease as shown by high response rates with aggressive induction therapies (e.g., combination of 5-FU, cisplatin and docetaxel, the results are poor at relapse. Despite progress in the primary treatment by combining chemotherapy, surgery, radiation therapy, and supportive care, the recurrence rate ranges from 35-50%. Patients usually relapse locally and develop symptoms such as difficulties in swallowing, eating and speaking. The median survival for patients with recurrent disease is six months and can reach 10 months in patients with good general status. Thus, improving the clinical benefit in patients with head and neck cancer is important to improve the patient's quality of life.
Currently, more effective and targeted treatments are needed for the treatment of cancers of the head and neck, particularly HNSCC.
It is believed that the combination of the compound of formula (I) and paclitaxel will provide improved and effective treatment as compared to each monotherapy for patients suffering from a cancer of the head and neck, particularly those suffering from a cancer of the head and neck or head and neck squamous cell carcinoma resistant to prior treatment with paclitaxel, fluorouracil (5-FU), platinum-based therapies, or a combination thereof.